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Cancer Cell：上海交大唐玉杰课题组发现儿童脑干胶质瘤DIPG的表观遗传靶向治疗新策略

2017-05-18 佚名 生物帮

脑干胶质瘤表观遗传
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近日，国际著名学术杂志《Cell》子刊、癌症研究领域顶级学术期刊《Cancer Cell》在线发表了上海交通大学医学院细胞分化与凋亡教育部重点实验室唐玉杰课题组与美国斯坦福大学医学院Michelle Monje实验室合作完成的题为“Tranional Dependencies in Diffuse Intrinsic Pontine Glioma ”的儿童脑瘤研究论文。肿瘤是目前儿童死亡的第二大原

近日，国际著名学术杂志《Cell》子刊、癌症研究领域顶级学术期刊《Cancer Cell》在线发表了上海交通大学医学院细胞分化与凋亡教育部重点实验室唐玉杰课题组与美国斯坦福大学医学院Michelle Monje实验室合作完成的题为“Tranional Dependencies in Diffuse Intrinsic Pontine Glioma ”的儿童脑瘤研究论文。

肿瘤是目前儿童死亡的第二大原因，其中儿童脑瘤的发病率排第二，仅次于儿童白血病。儿童脑干胶质瘤DIPG(Diffuse intrinsic pontine glioma)是发病率第二高的恶性儿童脑瘤类型，其预后极差，中位生存期仅为9个月左右，五年生存率低于百分之一，是造成儿童脑瘤病人死亡的主要原因之一。唐玉杰研究员近年来一直从事DIPG的表观遗传致病机制和靶向治疗的相关研究并取得一系列重要研究成果，证明了组蛋白介导的表观遗传调控异常在DIPG发病过程中具有重要功能并可作为有效治疗靶标。其中不仅揭示了约80% DIPG中携带的H3K27M组蛋白突变介导的表观遗传致病分子机制，为解析DIPG的发病机制开辟了表观遗传新方向(Cancer Cell. 2013 Nov 11；24(5)：660-72)；还发现了一个获FDA批准的表观遗传药物，组蛋白去乙酰化酶抑制分子(HDAC inhibitor，HDACi)panobinostat，能在预临床肿瘤模型中有效治疗DIPG，为DIPG的靶向治疗提供了表观遗传新思路(Nat Med. 2015 Jun；21(6)：555-9)。该药物目前已经进入I期人体临床试验，是根据预临床试验结果开展DIPG靶向药物临床试验的重大突破。

在最新发表的这份研究中作者发现DIPG肿瘤细胞对靶向抑制基因转录的BET inhibitor和CDK7inhibitor类表观遗传药物敏感，并且这两类药物均与panobinostat具有协同杀伤肿瘤的效果，进一步为DIPG提供了新的治疗策略。此外，作者还通过对病人来源的DIPG原代肿瘤细胞系进行超级增强子相关表观遗传分析发现该类肿瘤可能起源于少突胶质前体细胞(OPC，oligodendroglial precursor cells)，并进一步从肿瘤超级增强子调控基因中鉴定出重要的致癌分子机制和潜在药物靶标，尤其是意外的发现了钾离子通道和EPH受体等相关基因在DIPG肿瘤存活与侵袭中具有重要功能。该研究为深入理解DIPG的肿瘤发生机制和开发新的靶向治疗策略提供了重要的参考。

原始出处：

Surya Nagaraja， Nicholas A. Vitanza， Pamelyn J. Woo，et al.Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma.Cancer Cell. 2017 May 8

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    2018-04-28 xiaoshitou

    #治疗新策略#

    0

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    2017-10-21 12498e67m28暂无昵称

    #cancer cell#

    0

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    2018-03-24 zhaozhouchifen

    #Cell#

    0

  4. 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objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-09-02 维他命

    #CEL#

    0

  5. 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objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-20 12498568m52暂无昵称

    #新策略#

    0

  6. 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content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/IibQxuGJg8Nh1KeNMs1nZJeeldYs9olQSmfLFMSmc8OR6afKD5WrY1ktGibkd2ccEG1hMLcfjsTroQ86Z9scbvicQ/132, createdBy=3d661927529, createdName=Mr.Li先生, createdTime=Fri May 19 13:17:59 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199902, encodeId=ebc019990227, content=学习了分享了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=387d1660055, createdName=dhzzm, createdTime=Fri May 19 08:49:57 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199776, encodeId=1e8c199e76c1, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-20 一叶知秋

    #上海交大#

    0

  7. 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objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-20 12498bf3m30暂无昵称

    #DIPG#

    0

  8. 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objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19886, encryptionId=0ba81988692, topicName=上海交大)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Sat May 20 12:08:00 CST 2017, time=2017-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581565, encodeId=e8fd158156507, content=<a href='/topic/show?id=026059e658' target=_blank style='color:#2F92EE;'>#DIPG#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5976, encryptionId=026059e658, topicName=DIPG)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=508c16807186, createdName=12498bf3m30暂无昵称, createdTime=Sat May 20 12:08:00 CST 2017, time=2017-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199996, encodeId=f96319999679, content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/IibQxuGJg8Nh1KeNMs1nZJeeldYs9olQSmfLFMSmc8OR6afKD5WrY1ktGibkd2ccEG1hMLcfjsTroQ86Z9scbvicQ/132, createdBy=3d661927529, createdName=Mr.Li先生, createdTime=Fri May 19 13:17:59 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199902, encodeId=ebc019990227, content=学习了分享了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=387d1660055, createdName=dhzzm, createdTime=Fri May 19 08:49:57 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199776, encodeId=1e8c199e76c1, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-19 Mr.Li先生

    学习一下

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1748786, encodeId=fa3a1e4878678, content=<a href='/topic/show?id=233a64644ca' target=_blank style='color:#2F92EE;'>#治疗新策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64644, encryptionId=233a64644ca, topicName=治疗新策略)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a79236200456, createdName=xiaoshitou, createdTime=Sat Apr 28 14:08:00 CST 2018, time=2018-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780717, encodeId=b50c1e8071711, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, 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content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/IibQxuGJg8Nh1KeNMs1nZJeeldYs9olQSmfLFMSmc8OR6afKD5WrY1ktGibkd2ccEG1hMLcfjsTroQ86Z9scbvicQ/132, createdBy=3d661927529, createdName=Mr.Li先生, createdTime=Fri May 19 13:17:59 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199902, encodeId=ebc019990227, content=学习了分享了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=387d1660055, createdName=dhzzm, createdTime=Fri May 19 08:49:57 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199776, encodeId=1e8c199e76c1, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-19 dhzzm

    学习了分享了

    0

  10. 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content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/IibQxuGJg8Nh1KeNMs1nZJeeldYs9olQSmfLFMSmc8OR6afKD5WrY1ktGibkd2ccEG1hMLcfjsTroQ86Z9scbvicQ/132, createdBy=3d661927529, createdName=Mr.Li先生, createdTime=Fri May 19 13:17:59 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199902, encodeId=ebc019990227, content=学习了分享了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=387d1660055, createdName=dhzzm, createdTime=Fri May 19 08:49:57 CST 2017, time=2017-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=199776, encodeId=1e8c199e76c1, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Fri May 19 04:54:53 CST 2017, time=2017-05-19, status=1, ipAttribution=)]
    2017-05-19 飛歌

    学习了很有用

    0

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